Genistein Supplementation to Mitigate Cardiometabolic Dysfunction in Patients Undergoing Androgen Deprivation Therapy for Prostate Cancer (GeniPro)

Genistein is a natural supplement that comes from soy. The purpose of this study is to see if genistein has any effect on preventing or reducing heart disease and diabetes risk in men receiving Androgen Deprivation Therapy for prostate cancer. A combination of nutritional measures, blood markers and imaging tools will assess body composition, lipid levels and insulin resistance. Information from this pilot study will increase understanding of interventions which may prevent or reduce health risks during prostate cancer treatment. This project involves 24 men who will receive androgen deprivation therapy for prostate cancer.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Genistein; Drug: Placebo

Detailed Description

This is a double-blind, randomized, placebo-controlled trial of daily oral genistein in 24 men initiating Androgen Deprivation Therapy (ADT) for prostate cancer (PCa). Genistein is a natural supplement that comes from soy. The purpose of this study is to see if genistein has any effect on preventing or reducing heart disease and diabetes risk in men receiving ADT for PCa. A combination of nutritional measures, blood markers and imaging tools will assess body composition, lipid levels and insulin resistance. Information from this study will increase understanding of interventions which may prevent or reduce health risks during prostate cancer treatment.

All participants will receive standard counseling for diet and exercise by their oncology care team. Participants will be asked to withhold from any additional dietary supplements (with the exception of 1 standard daily multivitamin) during the study period. Participants will also be asked to complete a food diary for three days (on two weekdays and 1 weekend day).

Subjects will be randomized and stratified by diabetes status to either 60 mg/day oral genistein (30 mg taken twice daily), or matching placebo. The goal for randomizing based on diabetes status is to ensure approximately the same number of subjects who have diabetes and do not have diabetes receive genistein and placebo.

During follow-up, subjects will receive weekly reminders via phone call, text, or email to enhance compliance and monitor for potential adverse events. The 3-month study visit will be scheduled to coincide with the subject's standard of care follow-up visit. Three-month assessments will be the same as baseline assessments.

Investigators seek to assess indexes of insulin dynamics (insulin sensitivity and secretion) determined from an oral glucose tolerance test before and 12 weeks after a daily genistein or placebo supplement. Measures of vascular function before and 12 weeks after a daily genistein or placebo supplement will also be assessed via ultrasound along with other metabolic measures via blood draw.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Medical indication for androgen deprivation therapy (ADT) via luteinizing hormone-releasing hormone (LHRH) analog ± oral anti-androgen
• Diagnosis of prostate cancer
• ECOG performance status ≤ 2
• Life expectancy > 6 months
• Ability to provide informed consent

Exclusion Criteria:

• Transmural myocardial infarction, unstable angina, or congestive heart failure requiring hospitalization within the last 6 months
• Acute coronary event within the past month
• Use of intravenous antibiotics within the last 6 months
• Chronic liver disease
• Current use of cytotoxic or immunosuppressive drugs
• Chronic glucocorticoid or acute glucocorticoid or other synthetic steroid intake within the last month
• Chronic diarrhea or malabsorptive diseases (e.g., Crohn's disease)
• Stage 5 chronic kidney disease or need for hemodialysis
• Supplemental oxygen dependency
• Brain metastasis
• Severe cognitive dysfunction impairing ability to provide informed consent or consume study drug
• Dysphagia or requirement for artificial feeding
• Surgery or hospitalization within the last month
• Chemotherapy or radiation therapy within the last 60 days
• Insulin dependent diabetes
• HIV/AIDS
• History of organ transplant
• ECOG performance status > 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genistein; Participants with and without diabetes will receive 60 mg/day oral genistein (30 mg taken twice daily) for 12 weeks.	Drug: Genistein; Genistein is a natural supplement that comes from soy. Genistein will be taken orally (30 mg twice daily) for 12 weeks.
Placebo Comparator: Placebo; Participants with and without diabetes will receive placebo taken twice daily for 12 weeks.	Drug: Placebo; A placebo pill will be taken orally for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline	The Matsuda index is a measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Insulin sensitivity was calculated at baseline and after 8 weeks with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)]. Higher values are reflective of better insulin sensitivity. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin sensitivity or insulin resistance based on this index.	Baseline, Week 8 post-baseline
β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline	β-cell insulin secretion was determined from the OGTT. It is calculated as the ratio of the change in insulin values over the first 30 minutes of the OGTT and the change in glucose values over the first 30 minutes. Higher values are reflective of higher insulin secretion. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin secretion based on this index.	Baseline, Week 8 post-baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial Stiffness	Arterial stiffness will be assessed by applanation tonometry. Results will be reported in m/s (meters/seconds). A higher value indicates a worse outcome.	Baseline, Week 8
Vascular Endothelial Function at Baseline and Week 8 Post-baseline	Vascular endothelial function was measured with flow-mediated dilation (FMD in %) via ultrasound. A lower FMD indicates a worse outcome.	Baseline, Week 8 post-baseline

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Jessica Alvarez, PhD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): July 23, 2021
• Study Completion (Actual): July 23, 2021

Study Registration Dates

• First Submitted: May 6, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (Estimate): May 9, 2016

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Anticarcinogenic Agents; Phytoestrogens; Genistein
• Other Study ID Numbers: IRB00086186

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No